Sodium hydride → HCID 59699736, compound

HRID 1820051Notes

Reaction equation

HRID 1820051 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[H-].[Na+].[CH3:21][O:22][CH2:23][CH2:24][O:25][CH2:26]Cl>C1COCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])=[CH:9][N:8]([CH2:21][O:22][CH2:23][CH2:24][O:25][CH3:26])[C:5]2=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 24758Sodium hydride2×HCID 775901-(Chloromethoxy)-2-methoxyethane2×HCID 596997875-Bromo-3-(2-methoxyphenyl)-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 59699736HCID 59699736, compoundYield 95%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Under nitrogen 755 mg (2.49 mmol) of 5-bromo-3-(2-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridine was dissolved in 30 ml of anhydrous THF. 200 mg of sodium hydride were added and the resulting mixture was stirred at ambient temperature for 4 h. 0.5 ml of (2-methoxy-ethoxy)methyl chloride was added and the resulting mixture stirred at room temperature for 72 h. 0.75 ml of (2-methoxy-ethoxy)methyl chloride and an excess of sodium hydride were added and the reaction mixture allowed to stir at ambient temperature for am additional 4 h. 250 mg of tetra-n-butylammonium iodide were added and the reaction mixture stirred for 2 h at room temperature. The reaction was then quenched by addition of methanol and distributed between a saturated aqueous solution of ammonium chloride and dichloromethane. The aqueous phase was extracted with pyridinepethane and the combined organic phases dried over sodium sulfate and evaporated. The crude was then purified by chromatography on silica gel using a gradient of ethyl acetate in hexanes to afford 922 mg (2.36 mmol, 95% yield) of 5-bromo-1-(2-methoxy-ethoxymethyl)-3-(2-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridine as a yellow oil. 1H-NMR (d6-DMSO): δ8.40 (d, J=1.9 Hz, 1H), 8.17 (d, J=1.9 Hz, 1H), 7.97 (s, 1H), 7.52 (dd, J=1.3 Hz, 7.3 Hz, 1H), 7.34 (dd, J=1.4 Hz, 8.7 Hz, 1H), 7.15 (d, J=8.2 Hz 1H), 7.06 (t, J=7.3 Hz, 1H), 5.71 (s, 2H), 3.83 (s, 3H), 3.57 (m, 2H), 3.41 (m, 2H), 3.20 (s, 3H); MS: m/z 315, 317 [MH+-MeOC2H4O].

Workup

  1. stirringthe resulting mixture stirred at room temperature for 72 h
  2. stirringto stir at ambient temperature for am additional 4 h
  3. stirringthe reaction mixture stirred for 2 h at room temperature
  4. customThe reaction was then quenched by addition of methanol
  5. extractionThe aqueous phase was extracted with pyridinepethane
  6. dry with materialthe combined organic phases dried over sodium sulfate
  7. customevaporated
  8. customThe crude was then purified by chromatography on silica gel using a gradient of ethyl acetate in hexanes

Sources & evidence

ORD record
ord-85cdc7c305034966a0cb591ac2d4f73a
Source dataset
uspto-grants-2009_10
Patent number
US07601839B2

Reaction notes

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